Data show that cigarette smoking among high school students in the United States has increased from 27.5% in 1991 to 36.4% in 1997 (CD, 1998). Previous research has focused primarily on either social factors or psychological factors in youth smoking adoption, yet these data fail to explain fully why some youth can experiment with smoking yet not become established smokers, while others transition rapidly to a pattern of established smoking. Research on the genetic basis of smoking may shed some light on this question. We proposed a novel study of the genetic and non-genetic determinants of smoking adoption in high school students. This prospective cohort study will collect data on genetic and psychosocial factors in 1,200 9th graders and follow them over a four-year period (eight assessments) too assess initial smoking experiences and smoking patterns over time. The primary aim of the proposed study is to evaluate prospectively the contributions of specific genetic factors (i.e., genotypes for genes important in dopamine regulation) to the adoption of smoking. We will also evaluate whether these genetic effects are mediated by the rewarding effects of the initial smoking experience and/or by novelty-seeking personality. As a secondary aim, we will explore the main and interacting effects of other psychosocial factors (e.g., peer-family smoking, tobacco advertising, depression, alternate reinforcers) in the adoption of smoking. The data from this study can inform the development of programs to reduce the likelihood of adoption of an established pattern of smoking among adolescents and programs for smoking cessation treatment.